Infection caused by human herpes virus type 6: causes, symptoms, diagnosis, treatment

Herpesvirus type 6 is considered the most likely etiologic agent of multiple sclerosis, neonatal convulsive fever, and infectious mononucleosis, Epstein-Barr virus- and cytomegalovirus-negative infections, and HHV-6-associated encephalitis. HHV-6 is a cofactor in AIDS, some forms of cervical carcinoma, and nasopharyngeal carcinoma.

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Epidemiology of Human Herpes Virus 6 Infection

HHV-6, like other herpes viruses, is widespread. Antibodies are detected in the majority (>90%) of people over 2 years of age. At birth, most children are seropositive due to maternal antibodies, the titer of which decreases by 5 months. However, by one year, the ratio of seropositive to seronegative children is the same as in older children and adults. Maternal antibodies protect against HHV-6 infection in the first months of life, but after their titer decreases, the disease can manifest itself as fulminant exanthema. The virus is present in the human body in saliva and nasopharyngeal mucus, and in the latent phase it persists in monocytes/macrophages. Under natural conditions, the main route of transmission of the virus is airborne. Sexual transmission of the virus and perinatal infection are also possible. However, in most cases, infection occurs postnatally. It has been established that breast milk cannot be a transmission factor. Infection is possible through blood transfusions, organ transplants, and the use of medical instruments contaminated with the virus.

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What causes human herpes virus type 6 infection?

Human herpes virus type 6 (HHV-6) is similar to other herpes viruses, but differs from them in biological, immunological properties, spectrum of sensitive cells, antigen structure, genome composition, quantity and molecular weight of structural viral proteins. HHV-6 belongs to the subfamily Betaherpesvirinae, genus Roseolovirus.

The virion diameter is 160-200 nm, the symmetry type is ixahedral, the virus contains 162 capsomers, has a supercapsid lipid-containing membrane. The genome is represented by double-stranded DNA. Comparison of the primary structure of the genomes shows that HHV-6 is more similar to cytomegalovirus than to other herpesviruses.

Studies of HHV-6 isolates from people with various pathologies have shown that the viruses belong to variants A or B (HHV-6A and HHV-6B). Infection induced by HHV-6A is observed less frequently, and the role of this virus variant in human pathology is not clear enough, and HHV-6B is considered the main etiopathological factor of sudden exanthema (Exanthema subitum).

The HHV-6 virus is selectively tropic to CD4 T-cells, but is also capable of affecting T-cells with CD3, CD5, CD7, CD8 determinants. The virus replicates in many primary and continuous cell cultures of various origins: T-series lymphocytes, monocyte-macrophage, megakaryocytes, glial cells, thymus cells, and freshly isolated human lymphocytes. The growth cycle of the virus lasts 4-5 days.

Symptoms of Human Herpes Virus 6 Infection

The spectrum of diseases associated with HHV-6 is quite wide. HHV-6 is associated with various lymphoproliferative and immunosuppressive diseases, sudden exanthema of the newborn, malignant neoplasms, autoimmune pathology, some diseases of the central nervous system, etc.

Diseases associated with active HHV-6 infection

Diseases associated with primary acute HHV-6 infection	Diseases associated with persistent HHV-6 infection
Chronic fatigue syndrome (myalgic encephalomyelitis) Sudden exanthema in newborns and children (roseola infantum exanthema subitum) Infectious mononucleosis in adolescents and adults not associated with EBV infection Histiocytic necrotizing lymphadenitis (KiKuchis lymphadenitis)	Lymphoproliferative diseases (immunodeficiency, lymphadenopathy, polyclonal lymphoproliferation) Malignant lymphomas (non-Hodgkin's lymphoma, peripheral T-cell leukemia, B-cell lymphoma, dermatopathic lymphadenopathy, lymphogranulomatosis, sinusoidal B-cell lymphoma, pleomorphic T-cell lymphoma)

The etiologic role of HHV-6 in the development of sudden exanthema (synonyms: "pink rash of the newborn", "exanthema subitum", "roseola infantum", "sixth disease" ICD-10: B08.2) has been proven - a widespread disease of children aged 3 months to 3 years. The incubation period of the disease lasts 5-15 days. Exanthema subitum is characterized by an acute onset, high fever (38.5-40 C) and moderate intoxication. On the 4th day of the disease, the temperature decreases, and simultaneously or after a few hours, a macular rash appears. Usually, the rash is localized on the back, abdomen, chest, extensor surfaces of the limbs. The rash is rare on the face. After 2-3 days, the rash disappears, leaving no traces. Usually the disease ends without complications, but clinical cases of manifest infection have been described, which have various symptoms: fever above 40 °C, inflammation of the eardrum, respiratory and gastrointestinal symptoms, neurological complications (encephalitis, meningoencephalitis, serous meningitis, seizures). In rare cases, primary HHV-6 infection occurs with hepatosplenomegaly, fatal fulminant hepatitis, fatal disseminated infection.

Primary infection among adults is detected quite rarely, it manifests itself in the form of prolonged lymphadenopathy, mononucleosis-like syndrome, hepatitis, etc.

When examining peripheral blood, leukopenia, neutropenia, relative lymphocytosis and monocytosis are determined.

The role of HHV-6 as an AIDS cofactor is ensured by its ability to infect, replicate and destroy CD4 cells. An increase in the cytopathic effect is noted in dual infection compared to HIV-1 monoinfection, and HHV-6 can both inhibit and stimulate HIV-1 replication.

HHV-6 activates human papillomavirus oncoproteins E6 and E7 in cervical carcinoma.

HHV-6 DNA has been identified in tissues and cells from biopsy specimens of Hodgkin's lymphomas, mixed B- and T-cell non-Hodgkin's lymphomas, angioimmunoblastoid lymphadenopathy, African Burkitt lymphoma, T-cell acute lymphoblastoid leukemia, lymphogranulomatosis, non-Epstein-Barr virus-associated infectious mononucleosis, and a number of other lymphoproliferative disorders.

The role of HHV-6 in the development of chronic fatigue syndrome is still debated and requires further research.

Diagnosis of infection caused by human herpes virus type 6

Diagnosis of infection caused by human herpes virus type 6 is based on the use of immunological methods, electron microscopy and PCR.

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Treatment of infection caused by human herpes virus type 6

Treatment of infection caused by human herpes virus type 6 is symptomatic; gancinclovir has been proven to be effective.